1. Field of the Invention
The present inventions relate to photodynamic therapy and more particularly to dosimetry in photodynamic therapy.
2. Description of the Prior Art
Photodynamic therapy (PDT) requires the selective activation of a biological response, either in vivo or in vitro, by the absorption of light by photosensitive compounds which are selectively taken up or retained by the biological target or its immediate environment. The response obtained by PDT depends on many different parameters. These numerous parameters and their interdependence makes it difficult to optimize the PDT process in an individual application or a specific target in a given application. Even with the present lack of ability to accurately control the various parameters, PDT has been shown to be highly effective in the treatment of a variety of diseases including cancer and viral infections.
PDT begins with the administration of a given amount of photosensitizer which is selectively taken up and/or retained by the biologic target (i.e. tissue, cells, or biologic target). After the photosensitizers are taken up by the PDT target, a light of the appropriate wavelength to be absorbed by the photosensitizer is delivered to the targeted area. This activating light excites the photosensitizers to a higher energy state. The extra energy of the excited photosensitizer can then be used to generate a response in the target area. This can be through the process of heating, chemical reaction or acoustical effects.
The net effectiveness of the PDT process will be dependent on the amount of photosensitizer at the target, the absorption properties of the environment around the target and photosensitizer, and a number of physiologic factors such as temperature, pH, oxygen content, and the sensitivity of the target to the photosensitizer generated reaction. The dependence of the response on so many factors makes the optimization of the PDT extremely difficult and requires the process to be extensively researched prior to its use and still cannot account for variables arising from one application to the next or from one patient to the next. What is truly required is a system that can monitor the photoactivation process in real time so that the PDT process can be controlled and optimized for each individual application.
Of primary importance in obtaining a satisfactory PDT response is concentrating sufficient photosensitizer in the target and delivering sufficient light to the photosensitizer. Once the photosensitizer absorbs the activating light, and is therefor excited, its path of de-excitation is independent of the wavelength of excitation. For a given photosensitizer the amount of excited photosensitizer that will de-excite by a given pathway depends on the structure of the compound and its binding in the surrounding environment. The probability that the excited photosensitizer will de-excite by a specific pathway is described by its quantum yield for that pathway. One of the methods of photosensitizer de-excitation is the emission of fluorescence or phosphorescence, (i.e. the emission of a photon of a longer wavelength, different color). Almost all of the photosensitizer molecules used in PDT have quantum yields for fluorescence that are finite and will emit some fluorescence photons. The number of these fluorescence photons will be directly proportional to the number of excited photosensitizer molecules and therefore directly proportional to the excited photosensitizer concentration in the target tissue and the intensity of the excitation light incident of the target tissue, or (space irradiance).
The number of fluorescence photons will also be influenced by factors that quench the photosensitization process in the same manner. This dependence of the fluorescence on the product of photosensitizer concentration and space irradiance is identical to that of the therapeutic photochemical reaction. For that reason the measurement of fluorescence generated during the PDT process should be directly proportional to the amount of photosensitization reaction generated.